scholarly journals Insulin Attenuates the Insulin-Like Growth Factor-I (IGF-I)-Akt Pathway, not IGF-I-Extracellularly Regulated Kinase Pathway, in Luteinized Granulosa Cells with an Increase in PTEN

2009 ◽  
Vol 94 (6) ◽  
pp. 2184-2191 ◽  
Author(s):  
Akira Iwase ◽  
Maki Goto ◽  
Toko Harata ◽  
Sachiko Takigawa ◽  
Tatsuo Nakahara ◽  
...  
Keyword(s):  
Growth Factor ◽  
Granulosa Cells ◽  
Akt Pathway ◽  
Insulin Like Growth Factor ◽  
Factor I ◽  
Igf I ◽  
Growth Factor I ◽  
Kinase Pathway

Increased Expression of Insulin-Like Growth Factor I Is Associated with Ara-C Resistance in Leukemia.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 1513-1513
Author(s):  
Shori Abe ◽  
Hideo Harigae ◽  
Tadao Funato ◽  
Junichi Kameoka ◽  
Shinichiro Takahashi ◽  
...  
Keyword(s):  
Growth Factor ◽  
Biological Significance ◽  
Pi3 Kinase ◽  
Expression Level ◽  
Akt Pathway ◽  
Clinical Samples ◽  
Insulin Like Growth Factor ◽  
Factor I ◽  
Igf I ◽  
Growth Factor I

Abstract Cytosine arabinoside (Ara-C) is one of the most common drugs used in the treatment of acute myeloid leukemia (AML). Therefore, the resistance to Ara-C is a major obstacle to improvement of the cure rate of AML. However, the molecular mechanism for Ara-C resistance has not been fully understood. In order to investigate the mechanism involved in Ara-C resistance, the gene expression profile of Ara-C-resistant human K562 leukemia cells (K562/AC cells) was compared with that of the Ara-C-sensitive K562 parental cells by using a cDNA microarray platform. Correspondence analysis demonstrated that the insulin-like growth factor I (IGF-I) gene was significantly upregulated in K562/AC cells. The increased expression of IGF-I in K562/AC cells was confirmed by quantitative RT-PCR (RQ-PCR). We then studied the biological significance of IGF-I upregulation in Ara-C resistance. First, K562/AC cells were treated by suramin, a nonspecific growth factor antagonist. The treatment with suramine reduced viability and induced apoptosis of K562/AC cells. Furthermore, the addition of IGF-I neutralizing antibody exhibited the same effect as suramine. Moreover, the IC50 of Ara-C sensitive K562 parental cells was increased by the addition of exogenous IGF-I ligand. These results strongly suggest that IGF-I-IGF-I-R pathway is directly involved in Ara-C resistance. Next, the activation status of phosphatidylinositol 3-kinase (PI3-kinase)/Akt pathway, which is the downstream of IGF-I-IGFI-R signal, in K562/AC cells was examined. Western blot analysis showed that the phosphorylation level of Akt is higher in K562/AC cells than K562 sensitive cells. In addition, LY294002, the specific inhibitor for PI3-kinase reduced the survival of K562/AC cells. Since activation of PI3-kinase/Akt pathway has been shown to exhibit an anti-apoptotic effect in tumor cells, it is possible that IGF-I induces Ara-C resistance by escaping from apoptosis through PI3-kinase/Akt pathway in an autocrine or paracrine fashion. Finally, the expression level of IGF-I was examined in 27 clinical samples by RQ-PCR. The results showed that IGF-I expression level was higher in leukemic cells in refractory or relapsed AML patients, who received Ara-C combined chemotherapy, than that at diagnosis. These results suggest that the inhibition of the IGF-I-IGF-I receptor pathway is a valuable therapeutic approach to overcome Ara-C resistance in AML.

scholarly journals The Effect of Capsaicin on IGF-I and IGF-IR Expression in Ovarian Granulosa Cells

2020 ◽  
Vol 71 (1) ◽  
pp. 1977
Author(s):  
S. GULER ◽  
Β. ZIK
Keyword(s):  
Growth Factor ◽  
Granulosa Cells ◽  
Ovarian Development ◽  
Ovary Development ◽  
Insulin Like Growth Factor ◽  
Sprague Dawley ◽  
Factor I ◽  
Ovarian Granulosa Cells ◽  
Igf I ◽  
Growth Factor I

Capsaicin (trans-8-methyl-N-vanillyl-6-noneadamide) is a pungent ingredient in red peppers from the Capsicum family. Insulin-like growth factor-I (IGF-I) is expressed in granulosa cells and has an important role in ovarian development. However, there are no data about the IGF-I expression in ovarian granulosa cells after capsaicin treatment. The aim of this study was to investigate the expression of IGF-I and its receptor (insulin-like growth factor-I receptor [IGF-IR]) in primary rat ovarian granulosa cells after low and high doses of capsaicin treatment. For this, granulosa cells were isolated and cultured from ovaries of 30-day-old female Sprague-Dawley rats. Granulosa cell plates were divided into four groups as cell control (C), vehicle control (V), and 50 μM and 150 μM capsaicin groups. In experimental groups, granulosa cells were exposed to capsaicin for 24 hours and immunocytochemistry was performed afterwards using anti-IGF-I and anti-IGF-IR antibodies. Both IGF-I and IGF-IR expressions were found to be significantly increased in parallel to the capsaicin doses. Elevated levels of IGF-I may be a risk factor for ovarian development. Because of the crucial role of IGF-I in ovary development, capsaicin treatment can be effective on follicular development and/or disorders characterized by high IGF-I levels.

Co-ordinate actions of FSH and insulin-like growth factor-I on LH receptor expression in rat granulosa cells

1994 ◽  
Vol 141 (2) ◽  
pp. 301-308 ◽  
Author(s):  
M Kanzaki ◽  
M-A Hattori ◽  
R Horiuchi ◽  
I Kojima
Keyword(s):  
Growth Factor ◽  
Dna Synthesis ◽  
Granulosa Cells ◽  
Receptor Expression ◽  
Continuous Exposure ◽  
Insulin Like Growth Factor ◽  
Lh Receptor ◽  
Factor I ◽  
Igf I ◽  
Growth Factor I

Abstract The actions of FSH and Insulin-like growth factor-I (IGF-I) were studied in cultured rat ovarian granulosa cells. Cells became differentiated and expressed LH receptors when they were incubated for 72 h with 200 μg FSH/l (high FSH) but not 20 μg FSH/l (low FSH). Treatment with high but not low FSH increased the release of both immunoreactive and bioactive IGF-I into the medium. A combination of low FSH and IGF-I reproduced the effect of high FSH on LH receptor expression. We then examined the critical time when low FSH and IGF-I exerted their effects. In the presence of continuous low FSH, IGF-I was capable of inducing LH receptor expression even when added 24 h after the addition of low FSH. However, when IGF-I was added at 36 h, LH receptor expression measured at 72 h was greatly reduced. In contrast to the action of IGF-I, continuous exposure to low FSH was required for LH receptor expression, and IGF-I had no effect when FSH was not included for the entire 72 h of culture. DNA synthesis as assessed by both [3H]thymidine incorporation and nuclear bromodeoxyuridine labelling was moderate at the beginning of culture and markedly reduced at 24 h both in the presence and absence of either high FSH or low FSH plus IGF-I. In the presence of either high FSH or a combination of low FSH plus IGF-I, DNA synthesis remained decreased for up to 72 h whereas it began to increase in the absence of either high FSH or a combination of low FSH plus IGF-I. A similar increase in DNA synthesis was observed after 48 h when granulosa cells were treated with low FSH alone, which did not induce LH receptor expression. These results indicate that 1) growth and differentiation of granulosa cells are regulated inversely; 2) FSH and IGF-I act together to induce LH receptor expression; and 3) action of IGF-I is dependent on the presence of FSH. Journal of Endocrinology (1994) 141, 301–308

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